Neurosurgical Interventions for Neurotrauma in the Obstetric Population: A Systematic Review.

Trauma requiring neurosurgical intervention in the obstetric population is rare. Provision of care must include consideration for both maternal and fetal well-being, and conflicts may arise. Management strategies to reduce elevated maternal intracranial pressure (ICP) and provide adequate surgical exposure, for example, may compromise uteroplacental perfusion.

Spine tumor resection among patients who refuse blood product transfusion: a retrospective case series.

Study Objective: To describe the perioperative blood conservation strategies and postoperative outcomes in patients who undergo complex spinal surgery for tumor resection and who also refuse blood product transfusion.

Design: A retrospective case series.

Setting: A single-center, tertiary care and academic teaching hospital in Canada.

Scanning mutagenesis of the I-II loop of the Cav2.2 calcium channel identifies residues Arginine 376 and Valine 416 as molecular determinants of voltage dependent G protein inhibition.

Direct interaction with the beta subunit of the heterotrimeric G protein complex causes voltage-dependent inhibition of N-type calcium channels. To further characterize the molecular determinants of this interaction, we performed scanning mutagenesis of residues 372-387 and 410-428 of the N-type channel alpha1 subunit, in which individual residues were replaced by either alanine or cysteine. We coexpressed wild type Gbeta1gamma2 subunits with either wild type or point mutant N-type calcium channels, and voltage-dependent, G protein-mediated inhibition of the channels (VDI) was assessed using patch clamp recordings.

D2 dopamine receptors interact directly with N-type calcium channels and regulate channel surface expression levels.

N-type channels are located on dendrites and at pre-synaptic nerve terminals where they play a fundamental role in neurotransmitter release. They are potently regulated by the activation of a number of different types of pertussis toxin (PTX)-sensitive G alpha(i/o) coupled receptors, which results in voltage-dependent inhibition of channel activity via G betagamma subunits. Using heterologous expression in HEK 293T cells, we show via whole cell patch clamp recordings that D2 receptors mediate both G betagamma (i.

D1 receptors physically interact with N-type calcium channels to regulate channel distribution and dendritic calcium entry.

Dopamine signaling through D1 receptors in the prefrontal cortex (PFC) plays a critical role in the maintenance of higher cognitive functions, such as working memory. At the cellular level, these functions are predicated to involve alterations in neuronal calcium levels. The dendrites of PFC neurons express D1 receptors and N-type calcium channels, yet little information exists regarding their coupling.

Presynaptic calcium channels: structure, regulators, and blockers.

The central and peripheral nervous systems express multiple types of ligand and voltage-gated calcium channels (VGCCs), each with specific physiological roles and pharmacological and electrophysiological properties. The members of the Ca(v)2 calcium channel family are located predominantly at presynaptic nerve terminals, where they are responsible for controlling evoked neurotransmitter release. The activity of these channels is subject to modulation by a number of different means, including alternate splicing, ancillary subunit associations, peptide and small organic blockers, G-protein-coupled receptors (GPCRs), protein kinases, synaptic proteins, and calcium-binding proteins.

Differential role of N-type calcium channel splice isoforms in pain.

N-type calcium channels are essential mediators of spinal nociceptive transmission. The core subunit of the N-type channel is encoded by a single gene, and multiple N-type channel isoforms can be generated by alternate splicing. In particular, cell-specific inclusion of an alternatively spliced exon 37a generates a novel form of the N-type channel that is highly enriched in nociceptive neurons and, as we show here, downregulated in a neuropathic pain model.

Scanning mutagenesis reveals a role for serine 189 of the heterotrimeric G-protein beta 1 subunit in the inhibition of N-type calcium channels.

Direct interactions between the presynaptic N-type calcium channel and the beta subunit of the heterotrimeric G-protein complex cause voltage-dependent inhibition of N-type channel activity, crucially influencing neurotransmitter release and contributing to analgesia caused by opioid drugs. Previous work using chimeras of the G-protein beta subtypes Gbeta1 and Gbeta5 identified two 20-amino acid stretches of structurally contiguous residues on the Gbeta1 subunit as critical for inhibition of the N-type channel. To identify key modulation determinants within these two structural regions, we performed scanning mutagenesis in which individual residues of the Gbeta1 subunit were replaced by corresponding Gbeta5 residues.

A single Gbeta subunit locus controls cross-talk between protein kinase C and G protein regulation of N-type calcium channels.

The modulation of N-type calcium channels is a key factor in the control of neurotransmitter release. Whereas N-type channels are inhibited by Gbetagamma subunits in a G protein beta-isoform-dependent manner, channel activity is typically stimulated by activation of protein kinase C (PKC). In addition, there is cross-talk among these pathways, such that PKC-dependent phosphorylation of the Gbetagamma target site on the N-type channel antagonizes subsequent G protein inhibition, albeit only for Gbeta(1)-mediated responses.